[Liujunzi Decoction treats 4NQO-induced esophageal cancer in mice: a study based on serum metabolomics].

This study aims to explore the mechanism of Liujunzi Decoction in the treatment of 4-nitroquinoline-N-oxide(4NQO)-induced esophageal cancer in mice. One hundred mice of 35-45 days were randomized into blank, model, and low-, medium-, and high-concentration(18.2, 36.4, and 54.6 g·kg~(-1), respectively) Liujunzi Decoction groups. The mice in other groups except the blank group had free access to the water containing 100 µg·mL~(-1) 4NQO for 16 weeks for the modeling of esophageal cancer. The mice in the Liujunzi Decoction groups were fed with the diets supplemented with corresponding concentrations of Liujunzi Decoction. The body weight and organ weights were weighed for the calculation of organ indexes. The pathological changes of the esophageal tissue were observed by hematoxylin-eosin(HE) staining. Ultra performance liquid chromatography-mass spectrometry(UPLC-MS/MS) was employed to collect metabolites from mouse serum samples, screen out potential biomarkers, and predict related metabolic pathways. Compared with the blank group, the model group showed decreased spleen and stomach indexes and increased lung, esophagus, and kidney indexes. Compared with the model group, Liujunzi Decoction groups had no significant changes in the organ indexes. The HE staining results showed that Liujunzi Decoction inhibited the invasive growth and cancerization of the esophageal cancer cells. A total of 9 potential biomarkers of Liujunzi Decoction in treating esophageal cancer were screened out in this study, which were urocanic acid, 1-oleoylglycerophosphoserine, 11-deoxy prostaglandin E1, Leu-Glu-Lys-Glu,(±) 4-hydroxy-5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid, ureidosuccinic acid,(2R)-2,4-dihydroxy-3,3-dimethylbutanoic acid, kynurenic acid, and bicyclo prostaglandin E2, which were mainly involved in histidine, pyrimidine, alanine, aspartate, glutamate, pantothenate and tryptophan metabolism and coenzyme A biosynthesis. In summary, Liujunzi Decoction may exert the therapeutic effect on the 4NQO-induced esophageal cancer in mice by regu-lating the amino acid metabolism, inflammation, and immune function.

Deep learning-based characterization and redesign of major potato tuber storage protein.

Potato is one of the most important crops worldwide, to feed a fast-growing population. In addition to providing energy, fiber, vitamins, and minerals, potato storage proteins are considered as one of the most valuable sources of non-animal proteins due to their high essential amino acid (EAA) index. However, low tuber protein content and limited knowledge about potato storage proteins restrict their widespread utilization in the food industry. Here, we report a proof-of-concept study, using deep learning-based protein design tools, to characterize the biological and chemical characteristics of patatins, the major potato storage proteins. This knowledge was then employed to design multiple cysteines on the patatin surface to build polymers linked by disulfide bonds, which significantly improved viscidity and nutrient of potato flour dough. Our study shows that deep learning-based protein design strategies are efficient to characterize and to create novel proteins for future food sources.

Identification and map-based cloning of long glume mutant gene lgm1 in barley.

The spikes of gramineous plants are composed of specialized units called spikelets. Two bracts at the spikelet bases are known as glumes. The spikelet glumes in barley are degenerated into threadlike structures. Here, we report a long glume mutant, lgm1, similar in appearance to a lemma with a long awn at the apex. Map-based cloning showed that the mutant lgm1 allele has an approximate 1.27 Mb deletion of in chromosome 2H. The deleted segment contains five putative high-confidence genes, among which HORVU.MOREX.r3.2HG0170820 encodes a C2H2 zinc finger protein, an ortholog of rice NSG1/LRG1 and an important candidate for the Lgm1 allele. Line GA01 with a long glume and short awn was obtained in progenies of crosses involving the lgm1 mutant. Interestingly, lsg1, a mutant with long glumes on lateral spikelets, was obtained in the progenies of the lgm1 mutant. The long glume variant increased the weight of kernels in the lateral spikelets and increased kernel uniformity across the entire spike, greatly improving the potential of six-rowed barley for malting. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01448-x.

Clinical Effect of Rehabilitation New Fluid Combined with Sanjie Analgesic Capsules in the Treatment of Granulomatous Mastitis and Thyroiditis and Impact on Immune Indexes of Patients.

Objective: To analyze the clinical effect of rehabilitation new fluid combined with Sanjie analgesic capsules in the treatment of granulomatous lobular mastitis (GLM) and thyroiditis and the impact on immune indexes of patients. Methods: For a retrospective study, we selected 150 patients with GLM and 150 patients with thyroiditis admitted to The Fourth Hospital of Shijiazhuang from January 2021 to January 2022. We divided them into three groups based on the treatment methods. Control group 1 (CG1) included patients treated with rehabilitation new fluid alone, while control group 2 (CG2) included patients treated with the Sanjie analgesic capsules alone. The third group, the observation group (OG), included patients treated with rehabilitation new fluid (extract of drying body from Periplaneta americana) at an oral dose of 10 ml combined with Sanjie analgesic capsules. There were 50 patients in each group. The clinical efficacy, symptom improvement, the level changes of free triiodothyronine (FT3), free tetraiodothyronine (FT4), and thyroid stimulating hormone (TSH), and the changes of immune indexes such as CD4+ (cluster of differentiation 4+), CD25+ (cluster of differentiation 25+), CD68+ (cluster of differentiation 68+) and CD138+ (cluster of differentiation 138+) were analyzed. Results: After treatment, the total treatment effectiveness of GLM in the OG was 94%, which was significantly higher than 80% in the CG1 and 78% in the CG2 (P = .037, .021), while the total treatment effectiveness of thyroiditis in the OG was 92%, which was significantly higher than 76% in the CG1 and 74% in the CG2 (P = .029, 0.017). The scores of breast pain, breast overflow, tumor size, local skin changes, and axillary fossa lymphadenectasis of the affected side in the OG of GLM were better than those in CG1 (Pbreast pain < .001, 95%CI: 0.573-1.747; Pbreast overflow = .022, 95%CI: 0.074-0.905; Ptumor size = .008, 95%CI: 0.231-1.489; Plocal skin changes = .001, 95%CI: 0.382-1.498; Paxillary fossa lymphadenectasis of the affected side = .011, 95%CI: 0.096-0.704) and CG2 (Pbreast pain = .001, 95%CI: 0.449-1.711; Pbreast overflow = .049, 95%CI: 0.002-0.798; Ptumor size =0.019, 95%CI: 0.132-1.428; Plocal skin changes < .001, 95%CI: 0.563-1.517; Paxillary fossa lymphadenectasis of the affected side = .001, 95%CI: 0.202-0.678). The levels of FT3 and FT4 in the OG of thyroiditis were higher than CG1 (PFT3 < .001, 95%CI: 0.951-1.590; PFT4 < .001, 95%CI: 1.421-2.618) and CG2 (PFT3 < .001, 95%CI: 0.943-1.643; PFT4 < .001, 95%CI: 1.521-2.758), and the TSH level was lower compared with CG1 (PTSH < .001, 95%CI: 2.409-3.070) and CG2 (PTSH < .001, 95%CI: 2.540-3.230). The immune indexes of GLM were improved, and the levels of CD4+, CD25+, CD68+, and CD138+ in the OG were better than those in the CG1 (PCD4+ < .001, 95%CI: 2.967-4.912; PCD25+ < .001, 95%CI: 3.707-5.212; PCD68+ < .001, 95%CI: 1.445-2.200; PCD138+ < .001, 95%CI: 3.922-5.510) and CG2 (PCD4+ < .001, 95%CI: 3.093-4.995; PCD25+ < .001, 95%CI: 3.527-4.904; PCD68+ < .001, 95%CI: 1.334-2.216; PCD138+ < .001, 95%CI: 3.878-5.352). The immune indexes of thyroiditis were improved, and the levels of CD4+, CD25+, CD68+, and CD138+ in the OG were better than those in the CG1 (PCD4+ < .001, 95%CI: 4.235-6.117; PCD25+ < .001, 95%CI: 3.300-4.810; PCD68+ < .001, 95%CI: 1.173-1.939; PCD138+ < .001, 95%CI: 3.704-4.881) and CG2 (PCD4+ < .001, 95%CI: 3.136-5.422; PCD25+ < .001, 95%CI: 3.182-4.615; PCD68+ < .001, 95%CI: 1.216-2.113; PCD138+ < .001, 95%CI: 4.145-5.527). Conclusion: The clinical effect of rehabilitation new fluid combined with Sanjie analgesic capsule in the treatment of GLM and thyroiditis is remarkable, which enables enhancement of the treatment efficiency, and improves patients' clinical symptoms, functional indexes, and the levels of immune indexes, as a direction for the follow-up treatment in the clinic.

Projections from anteromedial thalamus nucleus to the midcingulate cortex mediate pain and anxiety-like behaviors in mice.

Prior research has demonstrated the involvement of the midcingulate cortex (MCC) and its downstream pathway in pain regulation. However, the mechanism via which pain information is conveyed to the MCC remains unclear. The present study utilized immunohistochemistry, chemogenetics, optogenetics, and behavior detection methods to explore the involvement of MCC, anteromedial thalamus nucleus (AM), and AM-MCC pathway in pain and emotional regulation. Chemogenetics or optogenetics methods were employed to activate/inhibit MCCCaMKIIα, AMCaMKIIα, AMCaMKIIα-MCC pathway. This manipulation evokes/relieves mechanical and partial heat hyperalgesia, as well as anxiety-like behaviors. In the complete Freund,s adjuvant (CFA) inflammatory pain model, chemogenetic inhibition of the AMCaMKIIα-MCCCaMKIIα pathway contributed to pain relief. Notably, this study presented the first evidence implicating the AM in the regulation of nociception and negative emotions. Additionally, it was observed that the MCC primarily receives projections from the AM, highlighting the crucial role of this pathway in the transmission of pain and emotional information.

Dissected Leaf 1 encodes an MYB transcription factor that controls leaf morphology in potato.

KEY MESSAGE: The transcription factor StDL1 regulates dissected leaf formation in potato and the genotype frequency of recessive Stdl1/Stdl1, which results in non-dissected leaves, has increased in cultivated potatoes. Leaf morphology is a key trait of plants, influencing plant architecture, photosynthetic efficiency and yield. Potato (Solanum tuberosum L.), the third most important food crop worldwide, has a diverse leaf morphology. However, despite the recent identification of several genes regulating leaf formation in other plants, few genes involved in potato leaf development have been reported. In this study, we identified an R2R3 MYB transcription factor, Dissected Leaf 1 (StDL1), regulating dissected leaf formation in potato. A naturally occurring allele of this gene, Stdl1, confers non-dissected leaves in young seedlings. Knockout of StDL1 in a diploid potato changes the leaf morphology from dissected to non-dissected. Experiments in N. benthamiana and yeast show that StDL1 is a transcriptional activator. Notably, by calculating the genotype frequency of the Stdl1/Stdl1 in 373-potato accessions, we found that it increases significantly in cultivated potatoes. This work reveals the genetic basis of dissected leaf formation in potato and provides insights into plant leaf morphology.

[Diterpenoid constituents in Pseudolarix amabilis and their antitumor activities in vitro].

By various chromatographic techniques and extensive spectroscopic methods, 17 abietane diterpenoids were isolated from the dichloromethane fraction of the 95% ethanol cold-soak extracts of the seeds of Pseudolarix amabilis, namely pseudoamaol A(1), 12α-hydroxyabietic acid(2), 12-methoxy-7,13-abietadien-18-oic acid(3), 13-hydroxy-8,11,13-podocarpatrien-18-oic acid(4), 15-hydroxy-7,13-abietadien-12-on-18-oic acid(5), 8(14)-podocarpen-13-on-18-oic acid(6), holophyllin K(7), metaglyptin B(8), 7α-hydroxydehydroabietinsaure-methylester(9), 7-oxodehydroabietic acid(10), 15-hydroxy-7-oxodehydroabietinsaure-methy-lester(11), 15-methoxydidehydroabietic acid(12), 7-oxo-15-hydroxy-dehydroabietic acid(13), 15-hydroxydehydroabietic acid(14), 8,11,13-abietatriene-15,18-diol(15), 8,11,13-abietatriene-15-hydroxy-18-succinic acid(16), and 7ß-hydroxydehydroabie-tic acid(17). Compound 1 was a new compound. The isolated compounds were evaluated for their antitumor activities(HepG2, SH-SY5Y, K562), and compounds 8 and 17 showed potential cytotoxic activity against K562 cells, with IC_(50) values of 26.77 and 37.35 µmol·L~(-1), respectively.

Transcriptomic and network pharmacology approaches revealed possible mechanisms underlying the 5-fluorouracil (5-FU)-sensitizing effect of Xuan-Fu-Hua decoction treatment on liver cancer cells.

Background: Xuan-Fu-Hua decoction is a traditional Chinese medicine formula widely used for the treatment of inflammation-related disease in the lung and liver. This study aimed to investigate the effect of Xuan-Fu-Hua decoction treatment on liver cancer cells and its mechanism of action. Methods: The impact of Xuan-Fu-Hua decoction treatment on the proliferation and apoptosis of SMMC-7721 liver cancer cells with or without 5-fluorouracil (5-FU) cotreatment was determined in both in vitro and in vivo settings. Alterations in gene expression patterns in SMMC-7721 cells induced by Xuan-Fu-Hua decoction treatment were explored by transcriptomic sequencing. Effective components of Xuan-Fu-Hua decoction and their target proteins were investigated using network pharmacology approaches. Results: Xuan-Fu-Hua decoction alone did not significantly influence SMMC-7721 liver cancer cell growth, but it significantly increased the 5-Fu-induced growth inhibition and apoptosis of SMMC-7721 liver cancer cells in vitro and in vivo. Most differentially expressed genes in SMMC-7721 liver cancer cells with or without Xuan-Fu-Hua decoction treatment were enriched in cell apoptosis-related pathways. Xuan-Fu-Hua decoction treatment significantly increased the transcription levels of DDIT3, PMAIP1, and ZMAT3 genes while decreasing that of WNT4, AXIN2, NFE2L2, TGFBR1, MITF, and IGFBP3 genes. An interaction network between the effective components and their possible target proteins was constructed by predicting compound-target protein and protein-protein interactions. Gene set enrichment analysis revealed the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway as well as Bcl-2 and Mcl-1 proteins as potential regulatory targets of Xuan-Fu-Hua decoction in sensitizing SMMC-7721 cells to the cytotoxicity of 5-FU treatment. Conclusions: Xuan-Fu-Hua decoction increased the sensitivity of liver cancer cells to the cytotoxicity of 5-FU treatment, possibly by potentiating cell apoptosis and inhibiting the prosurvival machinery.

[Polysaccharide of Atractylodis Macrocephalae Rhizoma inhibits expression of immune checkpoint PD-L1 by targeting miR-34a in esophageal carcinoma cells].

The immune checkpoint programmed cell death-ligand 1(PD-L1)-mediated immunosuppression is among the important features of tumor. PD-L1, an immunosuppressant, can induce T cell failure by binding to programmed cell death-1(PD-1). Thus, the key to restoring the function of T cells is inhibiting the expression of PD-L1. The Chinese medicinal Atractylodis Macrocephalae Rhizoma(AMR) has the anti-tumor, anti-inflammatory, antioxidant, and hypoglycemic activities, and the polysaccharide in AMR(PAMR) plays a crucial role in immunoregulation, but the influence on the immune checkpoints which are closely related to immunosuppression has not been reported. MicroRNA-34 a(miR-34 a) expression in esophageal carcinoma tissue is significantly lower than that in normal tissue. This study aims to investigate the inhibitory effect of PAMR on esophageal carcinoma cells, and the relationship between its inhibitory effect on PD-L1 expression and miR-34 a, which is expected to clarify the anti-tumor mechanism of PAMR. Firstly, different human esophageal carcinoma cell lines(EC9706, EC-1, TE-1, EC109 cells) were screend out, and expression of PD-L1 was determined. Then, EC109 cells, with high expression of PD-L1, were selected for further experiment. The result showed that PAMR suppressed EC109 cell growth. According to the real-time quantitative PCR(qPCR) and Western blot, it significantly suppressed the mRNA and protein expression of PD-L1, while promoting the expression of tumor suppressor miR-34 a. The confocal microscopy and luci-ferase assay proved that PAMR alleviated the inhibitory effect of PD-L1 while blocked miR-34 a. Additionally, the expression of PD-L1 was controlled by miR-34 a, and the combination of miR-34 a inhibitor with high-dose PAMR reversed the inhibitory effect of PAMR on PD-L1 protein expression. Thus, the PAMR may inhibit PD-L1 by increasing the expression of miR-34 a and regulating its downstream target genes. In conclusion, PAMR inhibits the expression of PD-L1 mainly by inducing miR-34 a.

The multi-omics basis of potato heterosis.

Heterosis is a fundamental biological phenomenon characterized by the superior performance of hybrids over their parents. Although tremendous progress has been reported in seed crops, the molecular mechanisms underlying heterosis in clonally propagated crops are largely unknown. Potato (Solanum tuberosum L.) is the most important tuber crop and an ongoing revolution is transforming potato from a clonally propagated tetraploid crop into a seed-propagated diploid hybrid potato. In our previous study, we developed the first generation of highly homozygous inbred lines of potato and hybrids with strong heterosis. Here, we integrated transcriptome, metabolome, and DNA methylation data to explore the genetic and molecular basis of potato heterosis at three developmental stages. We found that the initial establishment of heterosis in diploid potato was mainly due to dominant complementation. Flower color, male fertility, and starch and sucrose metabolism showed obvious gene dominant complementation in hybrids, and hybrids devoted more energy to primary metabolism for rapid growth. In addition, we identified ~2 700 allele-specific expression genes at each stage, which likely function in potato heterosis and might be regulated by CHH allele-specific methylation level. Our multi-omics analysis provides insight into heterosis in potato and facilitates the exploitation of heterosis in potato breeding.

[Chemical constituents of Physalis minima].

Fifteen compounds(1-15) were isolated from the 95% EtOH extract of the whole herb of Physalis minima by various chromatography techniques including silica gel, Sephadex LH-20, middle chromatogram isolated gel(MCI), octadecyl silica(ODS), and semi-preparative high performance liquid chromatography(HPLC). Their structures were elucidated by infrared spectroscopy(IR), ultraviolet spectroscopy(UV), high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), nuclear magnetic re-sonance(NMR), and circular dichroism(CD) as(5S)-5,11-dihydroxy-3-methyl-5-pentylfuran-2(5H)-one(1), withaphysalin R(2), withaphysalin Q(3), withaphysanolide A(4), phaseic acid(5), grasshopper ketone(6), 3S,5R-dihydroxy-6S,7-megastigmadien-9-one(7), vanillic acid(8), 2-trans,4-trans-abscisic acid(9), capillasterolide(10), 5,3'-dihydroxy-3,7,4'-trimethoxyflavone(11),(-)-loliolide(12), 4-hydroxyacetophenone(13), acetosyringone(14), and aurantiamide acetate(15). Compound 1 was a new butenolide, and compounds 5-7 and 10-12 were isolated from the Physalis for the first time. Compounds 4, 13, and 15 were isolated for the first time from P. minima. Moreover, their anti-inflammatory activity was evaluated in vitro. Compound 12 was found to possess an inhibitory effect on the transcription of an NF-κB-dependent reporter gene in LPS-induced 293 T/NF-κB-luc cells at 10 µmol·L~(-1), showing an inhibitory rate of 62.31%±4.8%.

The Taxus genome provides insights into paclitaxel biosynthesis.

The ancient gymnosperm genus Taxus is the exclusive source of the anticancer drug paclitaxel, yet no reference genome sequences are available for comprehensively elucidating the paclitaxel biosynthesis pathway. We have completed a chromosome-level genome of Taxus chinensis var. mairei with a total length of 10.23 gigabases. Taxus shared an ancestral whole-genome duplication with the coniferophyte lineage and underwent distinct transposon evolution. We discovered a unique physical and functional grouping of CYP725As (cytochrome P450) in the Taxus genome for paclitaxel biosynthesis. We also identified a gene cluster for taxadiene biosynthesis, which was formed mainly by gene duplications. This study will facilitate the elucidation of paclitaxel biosynthesis and unleash the biotechnological potential of Taxus.

A nonS-locus F-box gene breaks self-incompatibility in diploid potatoes.

Potato is the third most important staple food crop. To address challenges associated with global food security, a hybrid potato breeding system, aimed at converting potato from a tuber-propagated tetraploid crop into a seed-propagated diploid crop through crossing inbred lines, is under development. However, given that most diploid potatoes are self-incompatible, this represents a major obstacle which needs to be addressed in order to develop inbred lines. Here, we report on a self-compatible diploid potato, RH89-039-16 (RH), which can efficiently induce a mating transition from self-incompatibility to self-compatibility, when crossed to self-incompatible lines. We identify the S-locusinhibitor (Sli) gene in RH, capable of interacting with multiple allelic variants of the pistil-specific S-ribonucleases (S-RNases). Further, Sli gene functions like a general S-RNase inhibitor, to impart SC to RH and other self-incompatible potatoes. Discovery of Sli now offers a path forward for the diploid hybrid breeding program.

Genome design of hybrid potato.

Reinventing potato from a clonally propagated tetraploid into a seed-propagated diploid, hybrid potato, is an important innovation in agriculture. Due to deleterious mutations, it has remained a challenge to develop highly homozygous inbred lines, a prerequisite to breed hybrid potato. Here, we employed genome design to develop a generation of pure and fertile potato lines and thereby the uniform, vigorous F1s. The metrics we applied in genome design included the percentage of genome homozygosity and the number of deleterious mutations in the starting material, the number of segregation distortions in the S1 population, the haplotype information to infer the break of tight linkage between beneficial and deleterious alleles, and the genome complementarity of the parental lines. This study transforms potato breeding from a slow, non-accumulative mode into a fast-iterative one, thereby potentiating a broad spectrum of benefits to farmers and consumers.

Association of vitamin D levels and risk of latent tuberculosis in the hemodialysis population.

BACKGROUND: Vitamin D is essential in the host defense against tuberculosis (TB). Suboptimal vitamin D status is common in the hemodialysis population. Hemodialysis patients have an increased risk compared to the general population latent tuberculosis infection (LTBI). However, the association between vitamin D deficiency and LTBI in this population remains unclear. MATERIALS AND METHODS: We conducted a cross-sectional study between March and May 2017. Interferon-gamma release assay (IGRA) through QuantiFERON-TB Gold In-Tube was used to assess LTBI. Plasma 25-hydroxycholecalciferol (25-OHD) levels were measured by Elecsys Vitamin D Total assay. Suboptimal vitamin D levels included vitamin D insufficiency 20-29 ng/mg and vitamin D deficiency <20 ng/mL. Predictors for LTBI were analyzed. RESULTS: A total of 287 participants were enrolled. The suboptimal vitamin D level was 31.4% (90/287), which including the vitamin D deficiency was 13.9% (40/287). A total of 49.1% (141/287) people received nutritional vitamin D supplementation. The prevalence of IGRA positivity in this study was 25.1% (72/287). There was no significant difference in vitamin D concentrations or the proportion of vitamin D supplementation among the IGRA-positive and IGRA-negative groups (p = 0.789 and 0.496, respectively). In multivariate analysis, age >65 years old (odds ratio (OR), 1.89; 95% CI, 1.08-3.31; p = 0.026) and TB history (OR, 3.51; 95% CI, 1.38-8.91; p = 0.008) were independent predictors of IGRA positivity. CONCLUSION: This is the first study to report that vitamin D deficiency was not associated with IGRA positivity in a hemodialysis population. Aging and TB history were both independent predictors for LTBI.

Effect of timing of umbilical cord clamping on maternal and neonatal outcomes: A protocol for systematic review and network meta-analysis.

BACKGROUND: Umbilical cord clamping is one of the most commonly used medical or complementary medical interventions. The different timing of cord clamping may have any significant impact on public health. However, the results remain controversial. The aim of the study was to evaluate and compare the effect of different timing of umbilical cord clamping on maternal and neonatal outcomes. METHODS: A systematic literature search for relevant articles will be conducted in the Cochrane Central Register of Controlled Trials, PubMed, Embase, and Chinese Biomedical Literature Database from their inception to December 2018. Any randomized controlled trial (RCT), case-control study, observational study, that reported the effect of different timing of cord clamping will be included regardless of sample size. There are no language restrictions. Mortality and risk of iron-deficiency anemia will be used to assess the clinical effect. Risk of bias assessment of the included RCTs will be conducted by the Cochrane risk of bias tool and the Newcastle-Ottawa Scale is used to assess observational studies. All statistical analyses will be performed using Stata V.15.0. A modified version of Grades of Recommendation, Assessment, Development, and Evaluation will be used to assess the quality of evidence in network meta-analysis (NMA). RESULTS: The results will be published in a peer-reviewed journal. CONCLUSION: This will be the first NMA to evaluate and compare the effect of different timing of umbilical cord clamping. We hope that the results of this NMA will help clinicians and caregivers make more appropriate choices when clamping umbilical cord.

The genetic basis of inbreeding depression in potato.

Inbreeding depression confers reduced fitness among the offspring of genetic relatives. As a clonally propagated crop, potato (Solanum tuberosum L.) suffers from severe inbreeding depression; however, the genetic basis of inbreeding depression in potato is largely unknown. To gain insight into inbreeding depression in potato, we evaluated the mutation burden in 151 diploid potatoes and obtained 344,831 predicted deleterious substitutions. The deleterious mutations in potato are enriched in the pericentromeric regions and are line specific. Using three F2 populations, we identified 15 genomic regions with severe segregation distortions due to selection at the gametic and zygotic stages. Most of the deleterious recessive alleles affecting survival and growth vigor were located in regions with high recombination rates. One of these deleterious alleles is derived from a rare mutation that disrupts a gene required for embryo development. This study provides the basis for genome design of potato inbred lines.

Association of bacterial genotypes and epidemiological features with treatment failure in hemodialysis patients with methicillin-resistant Staphylococcus aureus bacteremia.

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) infections in the hemodialysis (HD) population are epidemiologically classified as healthcare-associated infections. The data about the clinical impact and bacterial characteristics of hospital-onset (HO)- and community-onset (CO)-MRSA in HD patients are scarce. The current study analyzed the difference in the clinical and molecular characteristics of HO-MRSA and CO-MRSA. METHODS: We performed a retrospective review and molecular analysis of clinical isolates from 106 HD patients with MRSA bacteremia from 2009 to 2014. CA genotypes were defined as isolates carrying the SCCmec type IV or V, and HA genotypes were defined as isolates harboring SCCmec type I, II, or III. RESULTS: CO-MRSA infections occurred in 76 patients, and 30 patients had HO-MRSA infections. There was no significant difference in the treatment failure rates between patients with CO-MRSA infections and those with HO-MRSA infections. CA genotypes were associated with less treatment failure (odds ratio [OR]: 0.18; 95% confidence interval [95% CI], 0.07-0.49; p = 0.001). For isolates with a vancomycin minimum inhibitory concentration (MIC) < 1.5 mg/L, the multivariate analysis revealed that HA genotypes and cuffed tunneled catheter use were associated with treatment failure. For isolates with a vancomycin MIC ≥1.5 mg/L, the only risk factor for treatment failure was a higher Pitt score (OR: 1.76; 95% CI, 1.02-3.05; p = 0.043). CONCLUSION: CA genotypes, but not the epidemiological classification of CO-MRSA, impacted the clinical outcome of MRSA bacteremia in the HD population.

The Genome of Medicinal Plant Macleaya cordata Provides New Insights into Benzylisoquinoline Alkaloids Metabolism.

The overuse of antibiotics in animal agriculture and medicine has caused a series of potential threats to public health. Macleaya cordata is a medicinal plant species from the Papaveraceae family, providing a safe resource for the manufacture of antimicrobial feed additive for livestock. The active constituents from M. cordata are known to include benzylisoquinoline alkaloids (BIAs) such as sanguinarine (SAN) and chelerythrine (CHE), but their metabolic pathways have yet to be studied in this non-model plant. The active biosynthesis of SAN and CHE in M. cordata was first examined and confirmed by feeding 13C-labeled tyrosine. To gain further insights, we de novo sequenced the whole genome of M. cordata, the first to be sequenced from the Papaveraceae family. The M. cordata genome covering 378 Mb encodes 22,328 predicted protein-coding genes with 43.5% being transposable elements. As a member of basal eudicot, M. cordata genome lacks the paleohexaploidy event that occurred in almost all eudicots. From the genomics data, a complete set of 16 metabolic genes for SAN and CHE biosynthesis was retrieved, and 14 of their biochemical activities were validated. These genomics and metabolic data show the conserved BIA metabolic pathways in M. cordata and provide the knowledge foundation for future productions of SAN and CHE by crop improvement or microbial pathway reconstruction.

JA, a new type of polyunsaturated fatty acid isolated from Juglans mandshurica Maxim, limits the survival and induces apoptosis of heptocarcinoma cells.

Juglans mandshurica Maxim (Juglandaceae) is a famous folk medicine for cancer treatment and some natural compounds isolated from it have been studied extensively. Previously we isolated a type of ω-9 polyunsaturated fatty acid (JA) from the bark of J. mandshurica, however little is known about its activity and the underlying mechanisms. In this study, we studied anti-tumor activity of JA on several human cancer cell lines. Results showed that JA is cytotoxic to HepG2, MDA-MB-231, SGC-7901, A549 and Huh7 cells at a concentration exerting minimal toxic effects on L02 cells. The selective toxicity of JA was better than other classical anti-cancer drugs. Further investigation indicated that JA could induce cell apoptosis, characterized by chromatin condensation, DNA fragmentation and activation of the apoptosis-associated proteins such as Caspase-3 and PARP-1. Moreover, we investigated the cellular apoptosis pathway involved in the apoptosis process in HepG2 cells. We found that proteins involved in mitochondrion (cleaved-Caspase-9, Apaf-1, HtrA2/Omi, Bax, and Mitochondrial Bax) and endocytoplasmic reticulum (XBP-1s, GRP78, cleaved-Caspase-7 and cleaved-Caspase-12) apoptotic pathways were up-regulated when cells were treated by JA. In addition, a morphological change in the mitochondrion was detected. Furthermore, we found that JA could inhibit DNA synthesis and induce G2/M cell cycle arrest. The expression of G2-to-M transition related proteins, such as CyclinB1 and phosphorylated-CDK1, were reduced. In contrast, the G2-to-M inhibitor p21 was increased in JA-treated cells. Overall, our results suggest that JA can induce mitochondrion- and endocytoplasmic reticulum-mediated apoptosis, and G2/M phase arrest in HepG2 cells, making it a promising therapeutic agent against hepatoma.